gdc-0449 and Muscle-Cramp

Until recently, advanced BCC were only accessible to a highly morbid surgery not necessarily proving to be carcinologic, and leaving terrible dysmorphic sequelae hard to accept by the patient. Another possibility, the only one in case of metastatic BCC, was chemotherapy which efficacy has never been proven in a clinical trial. Radiotherapy is most often not accessible because of previous radiotherapy or because of the localization or the extension of the lesion. The discovery of the importance of the sonic hedgehog pathway in the physiopathology of BCC has opened a new strategy with the development of targeted anti SMO drugs inactivating the pathway. Two molecules have become available following Phase I and II studies: vismodegib (Erivedge®) the first in class indicated for locally advanced and metastatic BCC and sonidegib (Odomzo®) indicated only for locally advanced BCC. The pharmacokinetic profiles of sonidegib and vismodegib showed several differences. No head to head comparative studies are available between these two drugs. Their pivotal phase II studies had similar study designs and endpoints. The objective response rate (ORR) by central review for vismodegib was 47.6% (95% CI 35.5-60.6) at 21 months follow-up. The ORR for sonidegib according to central review at 18 months follow-up is 56.1% (95% CI 43.3-68.3). Although both treatments share a similar adverse event profile with possible numerically differences in incidence, most patients will discontinue hedgehog inhibitors treatment in the long term because of side effects. Some resistant cases to these drugs have been described but are rather rare. In case of resistance or bad tolerability to the drug future hopes rely on immunotherapy currently under investigation. © 2018. Published by Elsevier Masson SAS. All rights reserved. Cet article fait partie du numéro supplément Prise en charge des carcinomes basocellulaires difficiles à traiter réalisé avec le soutien institutionnel de Sun Pharma.

Topics: Alopecia; Anilides; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Basal Cell Nevus Syndrome; Biphenyl Compounds; Carcinoma, Basal Cell; Cisplatin; Clinical Trials as Topic; Drug Resistance, Neoplasm; Dysgeusia; Fluorouracil; Hedgehog Proteins; Humans; Molecular Targeted Therapy; Multicenter Studies as Topic; Muscle Cramp; Mutation; Neoplasm Proteins; Patched-1 Receptor; Patched-2 Receptor; Pyridines; Signal Transduction; Skin Neoplasms; Smoothened Receptor

Topics: Adult; Aged; Amlodipine; Anilides; Antineoplastic Agents; Basal Cell Nevus Syndrome; Calcium Channel Blockers; Female; Humans; Male; Middle Aged; Muscle Cramp; Pyridines; Skin Neoplasms; Time Factors

Vismodegib is an oral hedgehog-pathway inhibitor approved for advanced basal cell carcinoma (BCC). Although most BCCs are amenable to surgery, excision of large tumors in aesthetically sensitive sites may compromise function or cosmesis.. We sought to evaluate the reduction in BCC surgical defect area after 3 to 6 months of neoadjuvant vismodegib.. This was an open-label, single-arm intervention trial with a primary outcome of change in target-tumor surgical defect area pre- and post-vismodegib (150 mg/d). Secondary outcomes were change in tumor area and tolerability.. Eleven of 15 enrolled patients, aged 39 to 100 years, completed the trial. Thirteen target tumors were excised after a mean of 4±2 months of vismodegib. In all, 29% (4 of 14 patients) could not complete more than 3 months because of vismodegib-related side effects. The mean baseline target-tumor diameter was 3.2 cm, and 10 of 13 tumors occurred on the face. Overall, vismodegib reduced the surgical defect area by 27% (95% confidence interval -45.7% to -7.9%; P=.006) from baseline. Vismodegib was not effective in patients who received less than 3 months. Over a mean follow-up of 11.5 (range 4-21) months for all tumors, only 1 tumor recurred at 17 months post-Mohs micrographic surgery.. Short follow-up time and no placebo control are limitations.. Neoadjuvant vismodegib appears to reduce surgical defect area when taken for 3 months or longer for nonrecurrent BCCs in functionally sensitive locations. Further studies with larger sample sizes and long-term follow-up are warranted.

Topics: Adult; Aged; Aged, 80 and over; Alopecia; Anilides; Antineoplastic Agents; Carcinoma, Basal Cell; Chemotherapy, Adjuvant; Dysgeusia; Female; Humans; Male; Middle Aged; Mohs Surgery; Muscle Cramp; Neoadjuvant Therapy; Pyridines; Skin Neoplasms; Tumor Burden

Topics: Anilides; Antineoplastic Agents; Carcinoma, Basal Cell; Humans; Muscle Cramp; Prospective Studies; Skin Neoplasms; Spasm

Topics: Aged; Anilides; Biphenyl Compounds; Carcinoma, Basal Cell; Dysgeusia; Female; Humans; Male; Middle Aged; Muscle Cramp; Nausea; Pyridines; Skin Neoplasms

Topics: Anilides; Antineoplastic Agents; Cannabis; Carcinoma, Basal Cell; Forehead; Humans; Male; Medical Marijuana; Middle Aged; Muscle Cramp; Neuromuscular Agents; Pyridines; Skin Neoplasms

Topics: Aged; Amitriptyline; Anilides; Female; Humans; Male; Middle Aged; Muscle Cramp; Muscle Relaxants, Central; Pyridines; Retrospective Studies